Purpose: To review studies which support the hypothesis that allograft inflammatory factor-1 (AIF-1), a protein initially identified in chronically rejected cardiac allografts, may be involved in the pathogenesis of the progressive fibroproliferative vasculopathy which is a hallmark of systemic sclerosis (SSc).

Recent findings: Recent findings demonstrated elevated AIF-1 expression both in SSc affected tissues and peripheral blood mononuclear cells. A detailed immunohistopathologic study examined the tissue and cellular localization of the protein in affected SSc tissues and demonstrated its expression in the endothelium of dermal and pulmonary vessels, in the pulmonary parenchyma, and in relevant inflammatory cells including T cells and macrophages. Furthermore, functional studies showed specific AIF-1 isoform expression stimulation by TGF-β.

Summary: This review summarizes recent findings suggesting that AIF-1 may play an important role in SSc vasculopathy and provides supporting evidence to consider the molecule as a novel therapeutic target.